Differential contribution of Ih to the integration of excitatory synaptic inputs in substantia nigra pars compacta and ventral tegmental area dopaminergic neurons

The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using in vitro and in vivo experiments, we determined that this navigation is the result of netrin 1 attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.

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Physiological Properties of Zebra Finch Ventral Tegmental Area and Substantia Nigra Pars Compacta Neurons

Journal of Neurophysiology ◽

10.1152/jn.01040.2005 ◽

2006 ◽

Vol 96 (5) ◽

pp. 2295-2306 ◽

Cited By ~ 43

Author(s):

Samuel D. Gale ◽

David J. Perkel

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Zebra Finch ◽

Dopaminergic Neurons ◽

Brain Slices ◽

Membrane Properties ◽

Substantia Nigra Pars Compacta ◽

D2 Dopamine Receptors ◽

Physiological Properties ◽

Ventral Tegmental

The neurotransmitter dopamine plays important roles in motor control, learning, and motivation in mammals and probably other animals as well. The strong dopaminergic projection to striatal regions and more moderate dopaminergic projections to other regions of the telencephalon predominantly arise from midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Homologous dopaminergic cell groups in songbirds project anatomically in a manner that may allow dopamine to influence song learning or song production. The electrophysiological properties of SNc and VTA neurons have not previously been studied in birds. Here we used whole cell recordings in brain slices in combination with tyrosine-hydroxylase immunolabeling as a marker of dopaminergic neurons to determine electrophysiological and pharmacological properties of dopaminergic and nondopaminergic neurons in the zebra finch SNc and VTA. Our results show that zebra finch dopaminergic neurons possess physiological properties very similar to those of mammalian dopaminergic neurons, including broad action potentials, calcium- and apamin-sensitive membrane-potential oscillations underlying pacemaker firing, powerful spike-frequency adaptation, and autoinhibition via D2 dopamine receptors. Moreover, the zebra finch SNc and VTA also contain nondopaminergic neurons with similarities (fast-firing, inhibition by the μ-opioid receptor agonist [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO)) and differences (strong h-current that contributes to spontaneous firing) compared with GABAergic neurons in the mammalian SNc and VTA. Our results provide insight into the intrinsic membrane properties that regulate the activity of dopaminergic neurons in songbirds and add to strong evidence for anatomical, physiological, and functional similarities between the dopaminergic systems of mammals and birds.

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Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat model

10.1101/714592 ◽

2019 ◽

Author(s):

Shawn Zheng Kai Tan ◽

Yasin Temel ◽

Ariel Yovela Chan ◽

Andrea Tsz Ching Mok ◽

Jose Angelo Udal Perucho ◽

...

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Rat Model ◽

Dopaminergic Neurons ◽

Chronic Treatment ◽

Periaqueductal Gray ◽

Substantia Nigra Pars Compacta ◽

Ventral Tegmental ◽

Positive Correlations ◽

Serotonergic Drugs

AbstractBackgroundElectrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful tool for modelling anticipatory fear and agoraphobia.MethodsIn this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then used tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons.ResultsAlthough acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, chronic administrations of both drugs were comparably effective. We found that the number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups. We showed a strong correlation between the number of dopaminergic neurons and freezing in the VTA. We further showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.LimitationsAlthough our data strongly hint to a role of dopaminergic mechanisms in the dlPAG induced fear response, more in-depth studies with larger sample sizes are needed to understand the neuronal mechanisms underlying the interactions between serotonergic drugs and dopaminergic cell number and fear behavior.ConclusionChronic treatment with an SSRI and a 5-HT1A agonist decrease the number of dopaminergic neurons in the VTA. These effects seem to be associated with reduced dlPAG-induced anticipatory freezing behaviour.Key PointsChronic treatment of escitalopram and buspirone was effective in reducing dlPAG induced anticipatory freezing behaviour.The number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups and was correlated to freezing.We found positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.

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Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats

Behavioural Brain Research ◽

10.1016/j.bbr.2007.07.002 ◽

2007 ◽

Vol 184 (2) ◽

pp. 133-141 ◽

Cited By ~ 89

Author(s):

Christine Winter ◽

Anke von Rumohr ◽

Adrian Mundt ◽

Dominique Petrus ◽

Julia Klein ◽

...

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dopaminergic Neurons ◽

Substantia Nigra Pars Compacta ◽

Ventral Tegmental

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The electrophysiological actions of dopamine and dopaminergic drugs on neurons of the substantia nigra pars compacta and ventral tegmental area

Life Sciences ◽

10.1016/0024-3205(92)90479-9 ◽

1992 ◽

Vol 51 (10) ◽

pp. 711-718 ◽

Cited By ~ 54

Author(s):

Nicola B. Mercuri ◽

Paolo Calabresi ◽

Giorgio Bernardi

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Substantia Nigra Pars Compacta ◽

Dopaminergic Drugs ◽

Ventral Tegmental

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Cardiovascular depressor responses to stimulation of substantia nigra and ventral tegmental area

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.6.h2549 ◽

1997 ◽

Vol 273 (6) ◽

pp. H2549-H2557 ◽

Cited By ~ 13

Author(s):

Gilbert J. Kirouac ◽

John Ciriello

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Intravenous Administration ◽

Dopaminergic Neurons ◽

Cardiovascular Responses ◽

Receptor Blocker ◽

Transitional Region ◽

Pars Lateralis ◽

Ventral Tegmental ◽

Stimulation Of

Experiments were done in α-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect ofl-glutamate (Glu) stimulation of the substantia nigra (SN) and ventral tegmental area (VTA) on arterial pressure (AP) and heart rate (HR). Glu stimulation of the SN pars compacta (SNC) elicited decreases in both mean AP (MAP; −18.9 ± 1.3 mmHg; n = 52) and HR (−26.1 ± 1.6 beats/min; n = 46) at 81% of the sites stimulated. On the other hand, stimulation of the SN pars lateralis or pars reticulata did not elicit cardiovascular responses. Stimulation of the adjacent VTA region elicited similar decreases in MAP (−18.0 ± 2.6 mmHg; n = 20) and HR (−25.4 ± 3.8 beats/min; n = 17) at ∼74% of the sites stimulated. Intravenous administration of the dopamine D2-receptor antagonist raclopride significantly attenuated both the MAP (70%) and the HR (54%) responses elicited by stimulation of the transitional region where the SNC merges with the lateral VTA (SNC-VTA region). Intravenous administration of the muscarinic receptor blocker atropine methyl bromide had no effect on the magnitude of the MAP and HR responses to stimulation of the SNC-VTA region, whereas administration of the nicotinic receptor blocker hexamethonium bromide significantly attenuated both the depressor and the bradycardic responses. These data suggest that dopaminergic neurons in the SNC-VTA region activate a central pathway that exerts cardiovascular depressor effects that are mediated by the inhibition of sympathetic vasoconstrictor fibers to the vasculature and cardioacceleratory fibers to the heart.

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Characteristics of Electrically Evoked Somatodendritic Dopamine Release in Substantia Nigra and Ventral Tegmental Area In Vitro

Journal of Neurophysiology ◽

10.1152/jn.1997.77.2.853 ◽

1997 ◽

Vol 77 (2) ◽

pp. 853-862 ◽

Cited By ~ 100

Author(s):

M. E. Rice ◽

S. J. Cragg ◽

S. A. Greenfield

Keyword(s):

Electrical Stimulation ◽

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dopamine Release ◽

Substantia Nigra Pars Compacta ◽

Frequency Dependent ◽

Body Regions ◽

Ventral Tegmental ◽

Da Release

Rice, M. E., S. J. Cragg, and S. A. Greenfield. Characteristics of electrically evoked somatodendritic dopamine release in substantia nigra and ventral tegmental area in vitro. J. Neurophysiol. 77: 853–862, 1997. Somatodendritic dopamine (DA) release from neurons of the midbrain represents a nonclassical form of neuronal signaling. We assessed characteristics of DA release during electrical stimulation of the substantia nigra pars compacta (SNc) in guinea pig midbrain slices. With the use of parameters optimized for this region, we compared stimulus-induced increases in extracellular DA concentration ([DA]o) in medial and lateral SNc, ventral tegmental area (VTA), and dorsal striatum in vitro. DA release was monitored directly with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Detection of DA in SNc was confirmed by electrochemical, pharmacological, and anatomic criteria. Voltammograms of the released substance had the same peak potentials as those of DA obtained during in vitro calibration, but different from those of the indoleamine 5-hydroxytryptamine. Similar voltammograms were also obtained in the DA-rich striatum during local electrical stimulation. Contribution from the DA metabolite 3,4-dihydroxyphenylacetic acid to somatodendritic release was negligible, as indicated by the lack of effect of the monoamine oxidase inhibitor pargyline (20 μM) on the signal. Lastly, DA voltammograms could only be elicited in regions that were subsequently determined to be positive for tyrosine hydroxylase immunoreactivity (TH-ir). The frequency dependence of stimulated DA release in SNc was determined over a range of 1–50 Hz, with a constant duration of 10 s. Release was frequency dependent up to 10 Hz, with no further increase at higher frequencies. Stimulation at 10 Hz was used in all subsequent experiments. With this paradigm, DA release in SNc was tetrodotoxin insensitive, but strongly Ca2+ dependent. Stimulated [DA]o in the midbrain was also site specific. At the midcaudal level examined, DA efflux was significantly greater in VTA (1.04 ± 0.05 μM, mean ± SE) than in medial SNc (0.52 ± 0.05 μM), which in turn was higher than in lateral SNc (0.35 ± 0.03 μM). This pattern followed the apparent density of TH-ir, which was also VTA > medial SNc > lateral SNc. This report has introduced a new paradigm for the study of somatodendritic DA release. Voltammetric recording with electrodes of 2–4 μm tip diameter permitted highly localized, direct detection of endogenous DA. The Ca2+ dependence of stimulated release indicated that the process was physiologically relevant. Moreover, the findings that somatodendritic release was frequency dependent across a range characteristic of DA cell firing rates and that stimulated [DA]o varied markedly among DA cell body regions have important implications for how dendritically released DA may function in the physiology and pathophysiology of substantia nigra and VTA.

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nNOS-Expressing Neurons in the Ventral Tegmental Area and Substantia Nigra Pars Compacta

eNeuro ◽

10.1523/eneuro.0381-18.2018 ◽

2018 ◽

Vol 5 (5) ◽

pp. ENEURO.0381-18.2018 ◽

Cited By ~ 9

Author(s):

Eleanor J. Paul ◽

Eliza Kalk ◽

Kyoko Tossell ◽

Elaine E. Irvine ◽

Nicholas P. Franks ◽

...

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Substantia Nigra Pars Compacta ◽

Ventral Tegmental

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Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons

Journal of Neurophysiology ◽

10.1152/jn.00760.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3388-3396 ◽

Cited By ~ 37

Author(s):

J. Russel Keath ◽

Michael P. Iacoviello ◽

Lindy E. Barrett ◽

Huibert D. Mansvelder ◽

Daniel S. McGehee

Keyword(s):

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dorsal Striatum ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Synaptic Modulation ◽

Afferent Projections ◽

Ventral Tegmental ◽

Midbrain Dopamine ◽

Da Release

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

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